Carotenoids are tetraterpene pigments whose de novo biosynthesis is restricted to plants and microorgamsms. Thus, humans obtain carotenoids in the diet by the ingestion of fruits and vegetables. Historically, it was thought that the most important role of some carotenoids in the human diet was their metabolic conversion to the essential micronutrient, vitamin A (retinol), and indeed, consumption of carotenoid-containing foods fulfills a significant part of the vitamin A requirement of many humans. More recently, other important roles for dietary carotenoids which are independent of their conversion to vitamin A have been suggested. In particular, recent studies suggest that carotenoids can inhibit both carcinogenesis and lipoprotein oxidation due to their intrinsic properties as fat soluble antioxidants. Thus carotenoids may help prevent both cancer and atherosclerotic heart disease. In spite of these potentially important roles in human health, little detailed information is available on the transport of carotenoids in human plasma. The objective of the present proposal is to define the transport systems for carotenoids in human plasma and the role of these compounds in preventing or retarding lipoprotein oxidation. Under AIM 1 we will determine the distribution of individual carotenoids among human plasma lipoproteins. This will be done by isolating lipoproteins, extracting carotenoids and quantitating them by high performance liquid chromatography. We will test the hypothesis that the lipid-soluble carotenoids will be associated with the plasma lipoproteins. Under AIM 2, we will explore the role of individual carotenoids in protecting plasma lipoproteins from oxidation. Isolated lipoproteins will be oxidized in vitro and the kinetics of disappearance of endogenous carotenoids and the appearance of oxidized lipids will be assessed by chemical analyses. The biological consequences of lipoprotein oxidation will be assessed using functional assays. We will test the hypothesis that oxidation of lipoproteins does not occur until endogenous carotenoids are destroyed. Under AIM 3 we will enrich the lipoproteins in individual carotenoids by oral ingestion of carotenoids and see if this leads to increased resistance of the lipoproteins to oxidative damage. We will test the hypothesis that increased consumption of carotenoids protects lipoproteins from oxidation.